The present invention relates to novel radiopharmaceutical imaging agents having non-stannous reductants. The present invention further relates to kits for forming radiopharmaceutical imaging agents, such kits including non-stannous reducing agents.
Several non-invasive methods of imaging skeletal structures, and body organs and tissues have been developed over the past decades. These methods are based on the tendency of the particular skeleton, organ or tissue to concentrate certain chemicals which may be detectable, such as through the use of scintiphotography or radiation detection. The use of radiopharmaceutical imaging agents in imaging skeletal structures, organs and tissues, is well known in the fields of biological and medical research as well as diagnostic evaluation procedures. Metal-based radiopharmaceuticals, such as those based on technetium have been found to provide particularly useful images of skeletal structures, and body organs and tissues from which diagnostic information may be obtained. More particularly, radiopharmaceuticals based on technetium 99m have been used successfully as diagnostic imaging agents.
In addition, metal-based radiopharmaceuticals, such as those based on rhenium have been found to be useful as therapeutic agents in the treatment of various diseases. More particularly, radiopharmaceuticals based on rhenium 186 or rhenium 188 have been used sucessfully as therapeutic agents.
The radiopharmaceutical agents generally include a metal radionuclide, various ligands for binding the radionuclide to the desired skeletal structure, organ or tissue, reducing agents, stabilizing agents, carriers and delivery vehicles suitable for injection into, or aspiration by a patient, etc.
Because of the relatively short half-lives of the metal radionuclide used in the radiopharmaceutical agent, it is desirable to provide the non-radioactive components of the agent as a kit to which a radionuclide containing solution may be added to form the agent. In particular, a radionuclide generator may be employed in a known manner to obtain a radionuclide which may then be combined and reacted with the contents of a kit which contains appropriate radiopharmaceutical forming components. For example, when forming a technetium imaging agent, a pertechnetate solution may be obtained from a technetium generator. The pertechnetate solution may then be combined and reacted with the components of a kit containing the other materials and agents necessary for forming the radiopharmaceutical agent.
A reducing agent is a necessary component of many radiopharmaceutical kits, the reducing agent acting to reduce the radionuclide containing solution, such as a pertechnetate solution, to obtain the final radiopharmaceutical agent. A reducing agent must be included in kits for the formation of technetium radiopharmaceuticals. Stannous ion is the most widely used reducing agent in kits for forming metal-based radiopharmaceuticals. This includes known kits for forming technetium 99m diagnostic agents for imaging the heart, kidney, lungs, and hepatobiliary system, as well as kits for imaging and therapeutic treatment of the brain and skeleton. However, the use of stannous ion as a reducing agent has several disadvantages generally arising from the inherent problems related to the complicated solid and solution chemistry of stannous compounds. In particular, the stannous ion is often a "non-innocent" reducing agent which interferes with or is incorporated into the final radiopharmaceutical.
Therefore it is desirable to provide radiopharmaceutical forming kits which contain non-stannous reducing agents.